Epoxides additions, lithium cuprate

Alkylation reactions reveal a mechanistic aspect of the cuprate reactions different from that of addition reactions. Theoretical analyses of reactions of alkyl halides (Mel and MeBr) [123, 124] and epoxides (ethylene oxide and cyclohexene oxide) [124] with lithium cuprate clusters (Me2CuLi dimer or Me2CuLi-LiCl, Scheme 10.11) resolved long-standing questions on the mechanism of the alkylation reaction. Density functional calculations showed that the rate-determining step of the... 

The related (Z)-lithium dialkenylcuprates (147) derived from acetylene itself also react well with epoxides to provide a useful route to (2)-homoallylic alcohols the lack of reactivity with esters allows an easy access to lactones (148) by condensations between epoxy esters and this type of cuprate (Scheme 29). Likewise, the lower homologs (149) and (151), both of which are relatively easy to prepare in optically active forms, can be readily converted into homoallylic and bishomoallylic alcohols (150) and (152) respectively. An ester unit can also be incorporated into the cuprate functions thus, addition of a mixed lithium cuprate, RCuYLi , to ethyl propiolate gives the cuprates (153), which add to epoxides to give unexpectedly the (Z)-crotonates (154). Such isomerization is not uncommon with vinyl carbanions in general, and is obviously a limitation when isomeric mixtures are produced. 

In Entry 5, the carbanion-stabilizing ability of the sulfonyl group enables lithiation and is then reductively removed after alkylation. The reagent in Entry 6 is prepared by dilithiation of allyl hydrosulfide using n-bulyl lithium. After nucleophilic addition and S-alkylation, a masked aldehyde is present in the form of a vinyl thioether. Entry 7 uses the epoxidation of a vinyl silane to form a 7-hydroxy aldehyde masked as a cyclic acetal. Entries 8 and 9 use nucleophilic cuprate reagents to introduce alkyl groups containing aldehydes masked as acetals. 

Related a,p-Unsaturated Esters. Similar a,p-unsaturated esters bearing a heterocyclic chiral auxiliary of a-amino acid origin at the p-position are known and have been utilized in asymmetric synthesis. Effective asymmetric conjugate additions of cuprates to (2), (3), and (5)J epoxidations of (3), and dipolar cycloadditions of (2) have been reported. Although oxazoli-dine (4) is only obtained as an 86 14 equilibrating mixture of stereoisomers, reactions with the lithium (Z)-enolate of methyl N-benzylideneglycinate (see Ethyl N-Benzylideneglycinate) are exclusively diastereoselective. 

As a consequence of the presumed irreversibility of die first step of the Peterson reaction, the stereochemistry of the elimination was determined solely by the relative rates (ki and ki ) of formation of threo- and erythro- -sHyl alkoxides (141) and (142), as indicated in Scheme 66. Support for the irreversibility of this step comes from the experiments on the nucleoidiilic opening of the diastereomeric epoxides (143) and (144). Thus, the syn- and onri-epoxides, when treated widi lithium dipropyl cuprate, yielded the threo- and erythro- -sHy alcohols (145) and (146), respectively. Treatment of die threo isomer with base gave the (Z)- ene exclusively and the erythro isomer gave the ( )-alkene. The high levels of selectivity for this elimination indicated diat die initial addition is not revenible. The elimina-... 

Vinyl copper derivatives such as 157 do not react with epoxides but transformation of the vinyl copper into a cuprate by the addition of pentynyl lithium gives a cuprate that preferentially transfers the vinyl group (the less stable anion is transferred from copper) to ethylene oxide to give the homoallylic alcohol39 -159. Note that 157 has the opposite stereochemistry to 149. 

The treatment of one equivalent of 5-lithio-2,3-dihydro-1,4-dioxin with 0.5 equivalent of copper(I) cyanide solubilized as its lithium chloride (0.5 equiv.) complex at — 15°C affords the corresponding cyanocuprate. The reactivity of this cuprate was assessed by its conjugate addition to cyclic enones, and by nucleophilic epoxide opening the presence of boron trifluoride etherate led to enhancement... 

Lithium n butyl (phenylthio) cuprate has been used in nucleophilic substitution reactions of arenesulfonyl fluorides, al-lylic acetates, 9 BBN, propargyllc carbamates, and bromo-alkenes, as well as in nucleophilic additions to acetoxy-epoxides. It Is a good choice for 1,4-addItIon of an n-Bu group, having been used in 1,4 addition-elimination reactions of a-oxoketene dithloacetals and 3-halo-2-cycloalkenones, and in tandem vicinal dialkylation reactions of 5-methyleneoxa-zolones and alkynes. A typical example Is the use of the reagentin the stereospecific synthesis of (, -2-heptenoicacidfrom acetylene (eq 1). ... 

Additions to Epoxides. Although the phenylthiocuprate is reported to be unreactive with cyclohexene epoxide, the homocuprate lithium bis(3,3-dlethoxy-l-propen-2-yl)cuprate and... 

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